The role of cyclic nucleotide-generating systems to the functional operation of the central nervous system is being investigated from a number of standpoints: l) The nature of the control of adenylate cyclase or phosphodiesterase activity by neurotransmitters, guanyl nucleotides, gangliosides, phospholipids, calcium ions, proteases and other factors. 2) The effect of intracellular GTP-levels on the responses of cyclic AMP-generating systems in brain slices. 3) The nature of synergistic interactions of biogenic amines such as norepinephrine, histamine, and serotonin with adenosine and the desensitization of receptor-adenylate cyclase complexes in slices and microsac preparations from brain. 5) The alterations in responsiveness of cyclic AMP-generating systems as result of prior treatment of animals with selected diets or drugs which will alter either specific neurotransmitter inputs or the disposition of calcium. 5) The relative importance of reuptake and deamination for the inactivation of adenosine in brain. 6) The development of selective agonists and antagonists for adenosine-receptor and the nature of the binding of such ligands to brain membranes.